A. Field of the Invention
The present invention generally relates to coating machines and, in particular, to fluid-bed coating machines used for the coating of tablets.
B. Description of the Prior Art
Tablets are formed by pressing pharmaceutically active drugs, filler and binding agents together. Once formed, it may be necessary, or desirable to provide the tablet with a coating which will:
1. prevent any portion of the drug from being released, such as in the form of dust;
2. mask any unpleasant odor or taste of the active drug, or any filler or binder used;
3. facilitate swallowing by providing a smoother and less absorbent outer layer;
4. protect the contents of the tablet from pre-mature digestion by providing a coating which is resistant to gastric fluids;
5. control the rate of absorption of the drug by the small intestine; and
6. improve the appearance of the tablet and provide a printable surface.
The tablets are generally coated using machines which spray a coating material, such as hydroxypropylmethylcellulose onto the surfaces of the tablets while the tablets are in motion within a product container. Two common types of machines tumble tablets within a horizontally rotatable drum during the spraying process, while another type of tablet coating machine uses a vertical flow of air to circulate tablets past a vertically disposed spray nozzle. The prior art coating machines are described below:
1. Dragee Kettle
For most applications, the exact thickness of the coated layer is not critical and many different types of coating machines may be used to apply a crude, yet effective coating to the tablet. An older once popular type of coating machine is called a dragee kettle and examples of these machines are disclosed in U.S. Pat. Nos. 3,831,262 and 5,334,244. This machine includes a large drum-like vessel which is typically rotated about a horizontal axis. The vessel includes a coating chamber which is partially filled with tablets to be coated so that as the vessel rotates, the tablets roll and tumble along the inside wall of the coating chamber. During this tumbling motion, coating materials in the form of aqueous or organic suspensions of liquids are sprayed through nozzles and into contact with the rolling tablets within the coating chamber. During the coating process, a current of temperature-controlled air circulates in the coating chamber of the dragee kettle, which helps evaporate the suspension agent of the coating material so that the coating material effectively dries and adheres to the tablets.
One problem with the dragee kettle coating machine is that typically the tablets are not the only surfaces coated within the coating chamber. Even when a carefully controlled spraying schedule is followed (such as spraying at very short intervals while the dragee kettle rotates), much of the sprayed coating material still ends up on the inside wall of the coating chamber, as well as throughout the evaporation/venting ducting. This over-spraying creates numerous contamination and cleaning problems, and further increases the cost of the coating since much of the coating material is lost during the coating process.
The above-described dragee kettle type coating machine is limited to coating tablets which do not require much precision in the thickness of the coated layer because the thickness of the coating of the tablets will vary in the same batch. This process may be used to coat many different types of pharmaceuticals, vitamins, and even candy, as long as uniform coating distribution and thickness are not required.
2. Perforated Pan
The next generation of tablet coating machines after the dragee kettle is called a perforated pall tablet coating machine. This machine has improved the tablet coating process and is the most common type of tablet coating machine in use today. The perforated pan machine includes a rotatable perforated drum which rotates about a horizontal axis within a housing, and further includes a plurality of nozzles positioned within the drum. The nozzles create a spray of coating material within the drum so that any tablets located within the drum will tumble about into and out of the spray pattern and, over a period of time, will accumulate a coating on their surface. An important improvement of the perforated pan coating machine over the dragee kettle is that the perforated pan machine allows air directed through the housing (using appropriate ducting) to pass through the perorated drum and quickly reach the tablets tumbling therein. The perforations of the drum effectively expose the tumbling tablets to the current of air, resulting in more uniform distribution of drying air for each tablet. The drum further includes solid baffles which are used to enhance mixing of the tablet bed in an effort to improve the distribution of the material being sprayed onto the tablets.
3. Fluidized Bed Coating Machines
Another type of particle-coating apparatus is called a fluidized bed coating machine (also known as a Wurster machine, after inventor Dale Wurster). Several examples of the Wurster coating machine are disclosed in U.S. Pat. Nos. 3,196,827,3,110,626, 3,880,116, 4,330,502, 4,535,006 and 5,236,503.
The Wurster coating machine is typically used to layer, coat or encapsulate lightweight powders, particles, granules or pellets of solid materials, including pharmaceutical drugs. Often, coatings are applied to modify the release of the substrate (protective barrier, taste masking, enteric coating, delayed release or sustained release). A predetermined quantity of these coated particles are usually packaged within an edible gelatin capsule or compressed into a tablet. The distribution uniformity of the applied substance may not be critical because the capsule or tablet contains multiple units and the average coating thickness of all of the pellets within the capsule dictate the average release properties and performance of the overall dosage form.
As described below, the Wurster machine generates an upward stream of air or other gases such as nitrogen to circulate a substrate (particles, pellets, powders, etc.) through a vertical spray of coating liquid within a product container. As the substrate cycles through the spray a minute amount of coating material is deposited on its surface. The number of cycles the substrate completes determines the thickness of the final coating layer.
The conventional Wurster machine works well when the particles are fine and lightweight (such as grains of powder). However, due to flow-related problems inherent in the design, the conventional Wurster machine fails to provide a uniform distribution of coating on heavier tablets because the heavier tablets do not uniformly cycle through the machine. The Wurster-coated tablets cannot be used for applications which require uniform, predictable and consistent distribution coatings on all tablets within a particular batch.
Certain types of pharmaceutical controlled-released tablets require high-precision coatings because the thickness of the coating governs the time of release and the release rate of the active ingredient of the tablet and thereby directly influences the effectiveness of the medication. The conventional Wurster machine is incapable of providing a high-precision coating on tablets, in part due to the following flow-related problems, each of which adversely effects the precision of the coating of each tablet or particle in the batch.
The conventional Wurster machine also creates undesirable turbulence and introduces high shear forces to the substrate as it cycles through the machine. The fine and lightweight substrates typically used with conventional Wurster machines are not adversely affected by the violent traumatic forces they must endure during each cycle. However, when a conventional Wurster machine is used to coat heavier tablets, the high shear forces generated during each coating cycle are capable of damaging the tablets and the resulting attrition rate of the tablets is unacceptable.
The heavier tablets are also more difficult to introduce into the high velocity airstream of the Wurster machine, usually causing some of the tablets to accelerate directly into hard structures within the machine, such as a nozzle assembly. The impact can easily shatter or otherwise damage the tablets.
Once a substrate is processed using the Wurster machine, the substrate must be removed from the product container. This is conventionally accomplished through a pivotal bottom door which, when opened, allows the coated substrate to simply fall by gravity into an awaiting and suitable container. Although this emptying process is effective, the process exposes both the substrate and the interior of the product container to the environment. Not only does this exposure introduce undesirable contamination to the product container, it also subjects the operators of the machine unnecessarily to potentially hazardous materials. To this end, it would be beneficial to remove the coated substrate from the coating machine using a more controlled and predictable process without undue complexity and without affecting the machine""s operation.
Another problem with Wurster machines is that they are relatively difficult to clean. The cleaning procedure typically requires the opening of the lower end of the product container and the application of an appropriate cleaning fluid. Some coating machines have spray nozzles within the coating machine to initially wash out any residual material deposited along the interior surfaces of the machine after the coating process. The cleaning fluid from these nozzles washes the interior surfaces of the machine and typically drains through the open lower end. Sometimes, however, the material being processed within the product container comprises a drug or other material which may be hazardous if accidentally inhaled, swallowed or even touched by personnel assigned to operate and clean the coating machine. It would therefore be beneficial to ensure that a maximum amount of this potentially hazardous residue is washed from the expansion chamber and the product container while isolating the contaminated waste from the surrounding environment. (i.e., without having to opening the machine).
It is an object of the present invention to provide a fluidized-bed type coating machine which overcomes the deficiencies of the prior art.
It is another object of the present invention to provide a Wurster-type coating machine which encourages even and predictable flow of tablets located in the down-bed.
It is another object of the present invention to provide a Wurster-type particle-coating machine which encourages tablets to flow radially inwardly along a distribution plate between the down-bed and an up-bed.
It is another object of the invention to provide a Wurster-type particle-coating machine which includes a central nozzle assembly located at the distribution plate for discharging a spray of coating liquid and which further includes structure to redirect tablets from the down-bed to the up-bed without impacting the central nozzle assembly.
It is another object of the invention to provide a Wurster-type particle-coating machine which is particularly suited to accurately coat heavier particles such as tablets.
It is another object of the present invention to provide a Wurster-type particle-coating machine which includes a partition which is shaped to provide an atraumatic transition of the tablets moving from the down-bed into the up-bed.
It is another object of the present invention to provide a Wurster-type particle-coating machine which cycles the tablets within the machine between the down-bed and the up-bed in a smooth, efficient, and consistent manner so that the resulting coating distribution of each tablet is consistent and predictable and tablet-attrition is minimized.
It is another object of the present invention to provide a Wurster-type particle-coating machine which permits discharge of the substrate (particles or tablets) through an opening at the center of the orifice plate at the base of the insert when multiple partitions are used.
It is another object of the present invention to provide a Wurster-type particle-coating machine which is easy to operate during the coating process and facilitates cleaning without disassembly of the Wurster insert.
The foregoing objects of the invention are met through various improvements to a Wurster-type fluidized bed apparatus for applying a coating liquid onto the surface of particles. The coating liquid is generally comprised of substances in a solution, suspension or dispersion in water or organic solvent (in some cases a molten liquid may be used). The apparatus includes a vertically disposed cylindrical or slightly conical product container having a peripheral wall, at least one cylindrical partition defining a centrally located up bed region and a peripherally located down bed region. The product container further includes an upper end connected to an expansion chamber and a lower end including an orifice plate having a plurality of openings for passage of fluidized air. A nozzle is centrally located through the orifice plate and is adapted to generate a spray of coating liquid upwardly into the up bed. Particles located within the product container circulate upwardly through the partition and the coating liquid spray, between the up bed and the down bed.
A feature of the invention comprises a nozzle ramp which is placed around the nozzle. The nozzle ramp is generally cusp shaped and includes a nozzle-ramp surface. The nozzle ramp is centrally positioned around the nozzle, and may be used within the product container with or without a nozzle sleeve. The nozzle ramp is directed upwardly towards the partition so that the nozzle-ramp surface directs particles moving generally horizontally across the orifice plate from the down bed upwardly into the partition and the up bed. The nozzle ramp may further include air passages for passing fluidized air upwardly to the nozzle-ramp surface. The air flow through these perforations provides a cushion of air at the surface of the nozzle ramp which minimizes the impact of tablets against this structure. One purpose of the perforated nozzle ramp is to atraumatically guide the horizontally flowing tablets vertically and upwardly into the up bed inside the partition.
A third feature of the invention comprises a nozzle ramp which is placed around the nozzle. The nozzle ramp is generally cusp shaped and includes a nozzle-ramp surface. The nozzle ramp is centrally positioned around the nozzle and is directed upwardly towards the partition so that the nozzle-ramp surface directs particles moving generally horizontally across the orifice plate from the down bed upwardly into the partition and the up bed. The nozzle ramp may further include air passages for passing fluidized air upwardly to the nozzle-ramp surface. The air flow through these perforations provides a cushion of air at the surface of the nozzle ramp which minimizes the impact of tablets against this structure. The purpose of the perforated nozzle ramp is to atraumatically guide the horizontally flowing tablets vertically and upwardly into the up bed inside the partition.